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Presentation and medical management of peripheral arterial disease in general practice: rationale, aims, design and baseline results of the PACE-PAD Study
Anja Neumann, Rebecca Jahn, Curt Diehm, Elke Driller, Franz Hessel, Gerald Lux, Oliver Ommen, Holger Pfaff, Uwe Siebert, Jürgen Wasem
To cite this version:
Anja Neumann, Rebecca Jahn, Curt Diehm, Elke Driller, Franz Hessel, et al.. Presentation and
medical management of peripheral arterial disease in general practice: rationale, aims, design and
baseline results of the PACE-PAD Study. Journal of Public Health, Springer Verlag, 2008, 17 (2),
pp.127-135. �10.1007/s10389-008-0223-8�. �hal-00478185�
ORIGINAL ARTICLE
Presentation and medical management of peripheral arterial disease in general practice: rationale, aims, design
and baseline results of the PACE-PAD Study
Anja Neumann
&Rebecca Jahn
&Curt Diehm
&Elke Driller
&Franz Hessel
&Gerald Lux
&Oliver Ommen
&Holger Pfaff
&Uwe Siebert
&Jürgen Wasem
&on behalf of the Patient Care Evaluation-Peripheral Arterial Disease (PACE-PAD) Study Investigators
Received: 24 April 2008 / Accepted: 5 August 2008 / Published online: 10 September 2008
# Springer-Verlag 2008
Abstract
Background Peripheral arterial disease (PAD) is highly prevalent among individuals of higher age or those with one or more cardiovascular risk factors. Screening for PAD is recommended, since it is often linked to atherothrombotic manifestations in the coronary or carotid circulation and associated with a substantial increase in all-cause and cardiovascular mortality. We aimed to assess patients with newly diagnosed, suspected and confirmed PAD in the primary care setting with regards to clinical characteristics,
diagnostic and therapeutic management (including referral to specialists), and medium-term outcomes.
Methods This was a multicentre, prospective, observational cohort study with a cross-sectional and a longitudinal part.
A total of 2,781 general practitioners across Germany were cluster randomised to document five consecutive patients each in one of the strata: (1) patients with intermittent claudication (IC) or other typical PAD-related complaints (group A) or (2) patients >55 years of age with one or more risk factors (group B) for PAD (current smoking, diabetes, previous myocardial infection and/or previous stroke).
Patients with confirmed PAD will be followed up for diagnostic procedures, therapy and vascular events over 18 months.
Results In group A, a total of 2,131 patients with suspected PAD (80.1% confirmed, 75.9% with referral to specialists) and in group B 9,921 patients were included (44.6%
confirmed, 54.6% referral). The ankle-brachial index was calculated in 41.3% and 33.5% only. Mean age was 66.6 years (group A) and 68.4 years (group B), respective- ly. Vascular risk factors were prevalent in both groups, in particular smoking (group A 44.6%, group B 44.4%), hypertension (73.2 and 78.1%), hypercholesterolaemia (64.6 and 70.6%) and diabetes mellitus (41.7 and 60.6%).
Concomitant atherothrombotic morbidities were frequent in both groups. In patients with the respective diseases, antihypertensive, antidiabetic, lipid-lowering and antith- rombotic therapies were prescribed in group A in 96.6, 96.0, 91.1 and 89.7% and in group B in 98.3, 97.4, 94.1 and 91.2%.
Conclusion The cross-sectional part of the study indicates a substantial burden of disease in PAD patients in primary The study group was supported by an advisory board founded in 2003
with the following members: Hans Jürgen Ahrens, Curt Diehm, Leonhard Hansen (until 2004), Klaus-Dieter Kossow.
A. Neumann : R. Jahn : F. Hessel : G. Lux : J. Wasem ( * ) Alfried Krupp von Bohlen und Halbach-Stiftungslehrstuhl für Medizin-Management, Universität Duisburg-Essen,
Schützenbahn 70, 45127, Essen, Germany
e-mail: anja.neumann@uni-essen.de C. Diehm
Klinikum Karlsbad Langensteinbach, Karlsbad, Germany
E. Driller : O. Ommen : H. Pfaff
Zentrum für Versorgungsforschung, Universität zu Köln, Cologne, Germany
U. Siebert
Department of Public Health,
Medical Decision Making and Health Technology Assessment, UMIT-University for Health Sciences,
Medical Informatics and Technology,
Hall, Austria
care. Treatment rates appear to have improved compared to earlier surveys. In the follow-up period, outcomes of these patients and their association with disease stages, guideline- oriented treatment or patient compliance and disease-coping strategies, among other factors, will be determined.
Keywords Peripheral arterial disease . Management . Vascular risk factors . Observational study .
Health care research
Background
Atherosclerotic cardiovascular disease remains the most common single cause of death in Germany and other Western countries (Statistisches Bundesamt 2006). Its three main manifestations comprise coronary heart disease (CDH), cerebrovascular disease (CVD) and peripheral arterial disease (PAD). The latter condition has been found to be highly prevalent in the general population and in primary care, respectively. For example, the getABI study in 6,880 patients aged 65 years and above found asymp- tomatic PAD as evidenced by a low ankle-brachial index (ABI) in 12.1%, and symptomatic PAD in 8.7% of patients (Diehm et al. 2004). Thus, only half of patients who present with objective evidence of PAD have clinically significant limb symptoms, such as walking impairment, intermittent claudication, ischaemic rest pain or non-healing wounds (Hirsch et al. 2006). The main medical problem of the PAD patient is not losing the lower extremity due to amputation, but rather to suffer a myocardial infarction or stroke (Heald et al. 2006). In view of the high disease burden of PAD with its associated risk of poor ischaemic outcomes, appropriate screening and intervention measures — including aggressive treatment of the common atherosclerotic risk factors—have been suggested repeatedly (Belch et al. 2003; Hirsch et al.
2006; Norgren et al. 2007).
While the necessity of such measures is widely undis- puted, the situation and management of PAD patients in primary care has been less well investigated. It may well differ between primary care setting across health care systems and countries (Hirsch et al. 2001b; Khan et al.
2007), and therefore extrapolation may not be possible. The primary care setting is of particular interest from a public health perspective, because the general physician serves as gatekeeper (Grumbach et al. 1999) with an important role in the case finding for PAD, referral to specialists to confirm or reject the suspected diagnosis and in the long- term management of these risk patients.
Against this background, the Patient Care Evaluation- Peripheral Arterial Disease (PACE-PAD) Study was initiated.
The present article describes the rationale, aims and methods of the study and the key findings of the cross-sectional part.
Methods
Aims and study hypotheses
The primary aim of the study is the description of the management (diagnostics and therapy) of patients with newly diagnosed, suspected or confirmed PAD, with particular focus on the interaction between general physi- cian and specialist care, depending on patient-related factors such as compliance with therapy and activity (coping with disease).
Secondary study aims are the investigation of the outcomes of guideline-oriented therapy on the incidence of cardiovascular, cerebrovascular or peripheral vascular events in patients with newly diagnosed PAD, depending on patient-related factors such as compliance and activity.
The following hypotheses will be tested: The cumulative incidence of cardiac, cerebrovascular and peripheral vascu- lar events during the follow-up period is lower:
1. In PAD patients with guideline-oriented management compared to PAD patients without such management 2. In PAD patients with high compliance compared with
those with low compliance
3. In PAD patients who are actively coping with their disease compared with patients who do not
Design and study flow
PACE-PAD is a multicentre, observational, non-interventional prospective study with pretest and pilot study periods, and in the main study, a cross-sectional part (all patients) and a longitudinal part with three visits over 18 months (for confirmed PAD patients in Fontaine stage I-IV only, see Fig. 1). Patients were assigned to two strata (symptomatic patients and patients with risk factors, both with suspected PAD).
A representative sample of ca. 43,500 physicians were contacted (general physicians or internists in primary care) throughout Germany. The “total design method” (Dillman 1991) for mail surveys was used with elements to ensure high acceptance rates. Basic elements include: minimisation of the burden on the respondent by designing question- naires that are attractive in appearance and easy to complete, printing mail questionnaires in booklet format, placing personal questions at the end, creating a vertical flow of questions and creating sections of questions based on their content; constructing a persuasive letter and using personalised communication; essential follow-up contacts of non-respondents (Dillman 1991). The questionnaire was pretested in terms of comprehensibility and feasibility with 12 randomly chosen physicians applying think aloud and probing techniques.
128 J Public Health (2009) 17:127 – 135
Physicians were assigned to one of two patient strata by means of cluster randomisation using a computer-generated randomisation list. They were requested to include consec- utively up to five eligible patients in the assigned stratum.
The study was conducted according to the principles of
“good epidemiological practice” (Arbeitsgruppe Epidemio- logische Methoden der Deutschen Arbeitsgemeinschaft Epidemiologie, DAE). Protection of patient and centre data was ensured. According to a statement of the legal department of the University Duisburg-Essen, for this non- interventional study a formal approval was not necessary.
Eligibility criteria
Patients were eligible for inclusion in group A if they hadnewly occurring intermittent claudication (IC) or claudication-like complaints with suspected PAD.
Patients with suspected PAD were eligible for inclusion in group B if they were aged 55 years or above and had (1) previous myocardial infarction and/or (2) previous ischae- mic stroke and/or (3) manifest type 1 or type 2 diabetes mellitus and/or (4) current smoking (for more than 10 years).
Patients were not eligible if they had PAD which had been diagnosed earlier.
Cross-sectional part
At inclusion the initials, birth date and gender of the patients were recorded. Further, type of insurance (private or general) and participation at a disease management program (diabetes mellitus type 1 or 2, coronary heart disease or other) were noted. Besides weight, height, systolic and diastolic blood pressure (method according to physician discretion), presence of complaints possibly associated with PAD (gluteal or leg pain when walking, reduced walk distance, ulceration or problems with leg wound healing), presence of risk factors for PAD (smoking, type 1 or 2 diabetes, arterial hypertension, hypercholester- olaemia and previously diagnosed carotid stenosis) were recorded, as were previous ischaemic manifestations [tran- sient ischaemic attack (TIA) or prolonged reversible ischaemic neurological deficit (PRIND), stable or unstable angina pectoris, including myocardial infarction] or inter- ventions [percutaneous transluminal coronary angioplasty (PTCA) with or without stenting, coronary artery bypass surgery (CABG), carotid revascularisation or stenting].
The general health state of the patient was rated by the physician on a 10-point numerical scale (1=extremely poor, 10=excellent). Similarly, compliance with therapy (1=
extremely poor, 10=excellent) as well as coping with disease (1=passive, 10=active) were assessed.
The following diagnostic procedures for PAD were recorded (by extremity, if applicable): leg pulse status at arteria (a.) femoralis, a. tibialis posterior, a. dorsalis pedis (normal, pathological, not assessed), auscultation of arter- ies, Ratschow test, measurement of walking distance, tiptoe exercise testing, Doppler-based measurement of the ABI, PAD stage according to Fontaine stage (if confirmed: I:
asymptomatic, IIa: mild claudication, IIb: moderate-severe claudication, III: ischaemic rest pain, IV: ulceration or gangrene), alternatively differential diagnosis of PAD or exclusion of PAD diagnosis in the office. Referrals were recorded, too (angiology, vascular surgery, neurology, orthopaedics, phlebology, radiology, other). In the case of referral to a vascular specialist, his/her diagnoses (PAD yes/
no, Fontaine stage, ABI and therapy) were recorded, too.
The following therapeutic measures were recorded:
specific exercise, drug therapy [prostaglandins, rheologic
agents (pentoxifylline, naftidrofuryl) or other] and planned
vascular surgery (revascularisation, peripheral bypass sur-
gery). Further detailed assessment of risk factor manage-
ment was performed: smoking cessation, antithrombotic
therapy (aspirin, ticlopidine, clopidogrel, other), anticoagu-
lation (unfractionated heparins, low molecular weight
heparins, heparinoids, vitamin K antagonists, other), lipid-
lowering measures (diet, statins, fibrates, other), antihyper-
tensive treatment (salt restriction, diuretics, calcium channel
blockers, beta blockers, alpha
1blockers, AT1 receptor
Fig. 1 Study design
antagonists, other), antidiabetic therapy (diet, insulin, oral antidiabetic drugs) or other and unspecified measures used for risk reduction.
Longitudinal study: endpoints at follow-up visits
The following endpoints will be recorded: myocardial infarction, stroke or minor/major amputation due to PAD.
Statistics
The sample size was calculated based on the assumption that the cumulative incidence of vascular events after 18 months is 6.8% in PAD patients with guideline-oriented therapy vs 9.8% in other PAD patients. Guideline-oriented therapy was defined by quality indicators that were determined by a standardised questionnaire. A sample of 3,483 symptomatic patients (of whom at least 85% were assumed to have diagnosed PAD) and of 20,485 patients with risk factors (of whom at least 10% were assumed to have diagnosed PAD) is required to obtain a power of 80%
at a significance level of 5%.
Using cross tables, frequency distributions and descriptive statistics, the distributions of variables between the two patient strata were compared. Additionally, a subgroup analysis of patients aged ≥55 years was performed. Throughout all analyses, a two-sided or the chi-square p value <0.05 (to evaluate differences between proportions for two or more than two groups) was considered to denote statistical significance. All analyses were performed with SPSS version 13 for Windows (SPSS Inc, Chicago, IL, USA).
Findings of the cross-sectional study
Characteristics Table 1 provides an overview of demograph- ic and clinical patient characteristics at inclusion. Mean patient age was somewhat lower in group A compared to group B (66.6 vs 68.4 years), as per definition in the latter group only patients aged 55 years and above were eligible. Male patients constituted about two thirds of the cohorts. While smoking was recorded in both groups with equal frequency, the other index risk factors current smoking, diabetes, hypertension and hypercholesterolaemia were more prevalent in group B, mostly with a long disease history. Previous ischaemic events (myocardial infarctions, stroke etc.), related interventions and current atherothrombotic manifestations (angina pectoris) were noted substantially more frequently in group B, but were also prevalent in group A.
Table 2 subdivides the patients in group A into those aged below 55 years and those aged 55 years and above, in order to enable direct comparison with the age-matched
group B. Compared to those patients aged ≥ 55 years, the younger patients in group A were less frequently current smokers, but included higher proportions of diabetic and hypercholesterolaemic individuals.
Diagnostics In group A, 80.1% of all included patients were finally assigned a PAD diagnosis and in group B 44.6% (Table 3). While the great majority of physicians reported that they applied basic diagnostic measures such as inspection, auscultation and leg pulse status (usually at three levels and on both sides), walking distance (57.3% in group A), tiptoe exercise testing (55.9% in group A) and Ratschow test (33.7% in group A) were done less frequently. The ABI was determined in 41.3 (group A) and 33.5% (group B) only.
Referrals While in group A three quarters were also seen by one or more specialists for further diagnostics or therapy, the proportion was much lower (only 54.6%) in group B (Table 4). If referred, patients in both groups were seen mostly by angiologists or vascular specialists.
Health status, coping, compliance The majority of patients were reported to be at an intermediate level of health status (ca. 60% in level 4 – 7 on the 10-point scale; Table 5). About a quarter of patients (27.8% in group A and 23.5% in group B) were reported to be passive. Compliance with diagnostics and therapy was predominantly intermediate or high.
Management Table 6 shows the patient management for diabetes, hypertension, hypercholesterolaemia and smoking in both strata. General advice about smoking cessation in current smokers and dietary advice in patients with elevated blood cholesterol level was frequent in both groups.
Treatment rates with blood pressure-lowering therapy in hypertensive patients were 96.6% in group A and 98.3% in group B. Likewise, treatment rates were also similar in both groups for diabetic patients (antidiabetic therapy in 96.0%
in group A and 97.4% in group B), as well as for lipid- lowering therapy in hyperlipidaemic patients (91.1% in group A and 94.1% in group B).
PAD The great majority of the PAD patients in both groups received antithrombotics or anticoagulants (89.7% of group A and 91.2% of group B; Table 7). Pain medication was prescribed in a quarter of group A and group B patients.
While there was a substantially lower proportion of training advice in group A (66.1 vs 71.4% in group B), in this group more prescriptions of rheologic agents (35.0 vs 31.1% in group B) and more planned vascular surgery interventions (23.3 vs 20.6% of group B) were reported. Both groups showed similar prescription prevalences of prostaglandins,
130 J Public Health (2009) 17:127 – 135
Table 2 Vascular risk factors (age ≥ or <55 years)
Vascular risk factors Group A (age ≥ 55) (n=1,808) Group B (age ≥ 55) (n =9,921) p value Group A (age <55) (n=323) None/1/2/3/4
a4.0/17.6/35.7/33.4/9.3 0.9/11.4/33.6/41.0/13.1 <0.05 5.3/27.2/26.9/29.7/10.8
Current smoking 39.4 (713) 44.4 (4,408) <0.05 73.7 (238)
>10 years 37.0 (669) 43.5 (4,318) <0.05 69.0 (223)
Diabetes mellitus 44.2 (800) 60.6 (6,010) <0.05 27.6 (89)
>10 years 22.1 (400) 50.4 (5,000) <0.05 8.4 (27)
Arterial hypertension 76.3 (1,379) 78.1 (7,751) 0.08 56.0 (181)
>10 years 51.4 (929) 57.2 (5,676) <0.05 20.4 (66)
Hypercholesterolaemia 66.1 (1,195) 70.6 (7,007) <0.05 56.3 (182)
>10 years 36.0 (651) 43.8 (4,346) <0.05 19.8 (64)
Carotid stenosis 9.2 (166) 8.7 (860) 0.47 4.0 (13)
Values indicate % (n)
a
Carotid stenosis excluded
Table 1 Patient characteristics in the two strata at inclusion
Parameter Group A (n=2,131) Group B (n =9,921) p value
Age (years), mean SD 66.6±11.1 68.4±8.0 <0.05
<55 15.1 (323) 0 (0) <0.05
55–64 24.2 (515) 34.9 (3,464) <0.05
65 – 74 35.5 (756) 41.5 (4,113) <0.05
75–84 21.8 (465) 21.4 (2,123) 0.66
85+ 3.4 (72) 2.2 (221) <0.05
Males:females, % 63.9:36.1 67.5:32.5 <0.05
Body mass index 27.7±4.5 28.5±6.9 <0.05
Systolic and diastolic BP 140.4/82.6 139.1/81.2 <0.05
Complaints: yes 98.7 (2,103) 51.7 (4,576) <0.05
Vascular risk factors
None/1/2/3/4
a4.2/19.1/34.4/32.8/9.5 0.9/11.4/33.6/41.0/13.1 <0.05
Current smoking 44.6 (951) 44.4 (4,408) 0.89
>10 years 41.9 (892) 43.5 (4,318) <0.05
Diabetes mellitus 41.7 (889) 60.6 (6,010) <0.05
>10 years 20.0 (427) 50.4 (5,000) <0.05
Arterial hypertension 73.2 (1,560) 78.1 (7,751) <0.05
>10 years 46.7 (995) 57.2 (5,676) <0.05
Hypercholesterolaemia 64.6 (1,377) 70.6 (7,007) <0.05
>10 years 33.6 (715) 43.8 (4,346) <0.05
Carotid stenosis 8.4 (179) 8.7 (860) 0.73
Earlier ischaemic events
None/1/2/3/4/5/missing 61.2/21.5/11.5/4.5/0.9/0.2/0.2 38.5/23.4/25.6/10.1/2.0/0.4/0.0 <0.05
Cerebrovascular: any 13.7 (293) 24,0 (2,377) <0.05
TIA/PRIND 10.7 (228) 14.4 (1,433) <0.05
Ischaemic stroke 6.0 (127) 19.3 (1,913) <0.05
Coronary: any 31.3 (667) 47.4 (4,705) <0.05
Stable AP 26.4 (562) 34.9 (3,465) <0.05
Instable AP 6.7 (142) 12.2 (1,207) <0.05
Myocardial infarction 12.5 (267) 34.7 (3,445) <0.05
Coronary interventions
None 80.3 (1,711) 69.7 (6,917) <0.05
Percutaneous transluminal coronary angioplasty (PTCA) 11.4 (243) 19.1 (1,897) <0.05
Coronary artery bypass surgery (CABG) 6.9 (146) 12.5 (1,243) <0.05
Carotid surgery 2.9 (62) 2.9 (289) 0.99
Other 2.4 (52) 1.7 (165) <0.05
Values indicate % (n)
a
Carotid stenosis excluded
recommended bed rest, recommended posture of legs, wound treatment and antibiotics.
Fontaine stages In group B, there were significantly more asymptomatic PAD patients than in group A, while there were significantly more PAD patients in group A in higher stages (Table 8).
Table 3 Diagnostics to confirm or reject the PAD diagnosis in the two strata
Frequency of diagnostics
Group A (n=2,131)
Group B (n =9,921)
p value
Inspection 87.4 (1,863) 89.9 (8,921) <0.05 Pathological 32.7 (696) 17.6 (1,745) <0.05 Ambilateral pulse
status at 3 levels
a86.0 (1,833) 83.7 (8,304) <0.05 Any level pathological 81.7 (1,740) 48.8 (4,843) <0.05 Auscultation 61.6 (1,313) 64.0 (6,349) <0.05 Pathological 26.5 (564) 16.1 (1,602) <0.05 Ratschow test 33.7 (719) 31.6 (3,136) 0.06
Pathological 21.7 (462) 12.6 (1,250) <0.05 Walking distance 57.3 (1,221) 44.2 (4,390) <0.05 Pathological 48.9 (1,041) 25.1 (2,487) <0.05 Tiptoe posture 55.9 (1,191) 51.1 (5,068) <0.05 Pathological 27.1 (577) 14.2 (1,410) <0.05 ABI measurement 41.3 (880) 33.5 (3,321) <0.05
≤ 0.9 29.0 (618) 17.0 (1,690) <0.05
Other 5.2 (111) 4.5 (444) 0.15
PAD diagnosed
b80.1 (1,706) 44.6 (4,423) <0.05 Values indicate % (n)
a
A. femoralis, a. tibialis posterior, a. dorsalis pedis, both legs each
b
